The tissue-specific, compensatory expression of cyclooxygenase-1 and -2 in transgenic mice

Prostaglandins Other Lipid Mediat. 2002 Feb;67(2):121-35. doi: 10.1016/s0090-6980(01)00177-0.


Prostaglandins are essential regulators of tissue homeostasis, reproduction and inflammation. We have recently shown that cells derived from cyclooxygenase (COX)-deficient mice express higher, compensatory levels of the remaining COX isozyme [Kirtikara et al., J. Exp. Med., 187, 517 (1998)]. To assess this compensatory expression phenomenon in vivo, we quantified COX-1 and COX-2 mRNA levels in various organs of COX-1- and COX-2-ablated mice using a reverse transcriptase-polymerase chain reaction (RT-PCR) method. We found that COX-1 and COX-2 mRNAs in the brains of COX-ablated mice were elevated > 2-fold compared with wild-type (WT) animals. COX-2 mRNA was enhanced approximately 2-fold in the kidneys and stomachs of COX-1-deficient mice while COX-1 expression remained unchanged. Conversely, the livers of COX-2-deficient mice expressed 15-fold higher COX-1 mRNA levels, while hepatic COX-2 mRNA levels were not significantly altered in the COX-1-ablated mice. Steady state levels of COX-1 and COX-2 mRNAs in the hearts, lungs and spleens of WT, COX-1- and COX-2-deficient mice were indistinguishable from each other. Peritoneal macrophages isolated from COX-1- and COX-2-ablated mice also expressed significantly higher steady-state levels of cytoplasmic phospholipase A2 and 5-lipooxygenase mRNAs suggesting a global upregulation of eicosanoid biosynthetic pathways in COX-deficient mice. These data suggest that expression of both COX-1 and COX-2 can be re-programmed to compensate for the lack of both alleles of the alternate COX gene in transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Gene Deletion
  • Gene Expression Profiling
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Organ Specificity
  • Phospholipases A / genetics
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Prostaglandin-Endoperoxide Synthases / deficiency
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Phospholipases A
  • Phospholipases A2